Growth Hormone Axis Research Articles

Neuroscience - Lagree Method - Manual Medicine Physical Exercise, Microformer, Psycho-Body Massage, Emotional-Affective And Socio-Relational Recovery

Exercise as a moment of socializing, fun and well-being. Titanic Enterprise? Just want to do. For me, I have brought together the greatest, the best, my closest friends, for one great passion: movement, physical exercise, as a source of well-being, especially in this critical moment for those who have suffered damage even from the point of view. economically. But the topic is another. I was in Sicily, a friend of mine is training with others but ... he has a herniated disc ... prevents him from moving ... yet, thanks also to the encouragement, the sociability, the fun of the group itself, he does not he feels pain and is able to perform all exercises perfectly. Hence the idea: can conviviality, sociality in the world of sport have and be a natural opioid? Can we modulate our perception of pain thanks to a “disembodied attitude and an enactive approach? We are embodied beings” , in which minds, bodies, environment and culture are connected to each other on different levels. “The answer is yes and the purpose of the post is to leave you breathless to admire the infinite beauty of my friends who train and have fun, live the sport , the Movement and long live true friendship. Obviously I emphasize my world, my fitness lagree method, Lagreefitness which also improves self-esteem, good mood through the generation of wellness molecules and hormones. heart health, brain health, muscle and joint health. Neuroscience and lagree method; induction of the pituitary hypothalamic axis of growth hormone, its possible implications in longevity The massage or touch is to give well-being through touch, body. A well-being not only physical, but also neural, social, rewriting neuronal circuits and improving synaptic plasticity. With this image I want to highlight the art of massage, manual techniques, rehabilitation and also movement and psychology. In a moment of uncertainty I want to give certainties; what we will return to instill well-being again. this is the topic of our research. indeed two. we scientifically demonstrate how both the massage and the Lagree method are fundamental for a better cognitive development, so please send me the material in private. If you want you can; you are a thinking being and while you think, think big. Imagine, create, thrill and expand. Reinvent yourself by creating the best version of yourself. Now imagine and create the desired reality. The amygdala, an almond-shaped group of nuclei located in the limbic system, deep within the medial temporal lobes of the brain, is the boss when it comes to processing and storing memories of various emotions. In fact, the amygdala experiences emotions even before the conscious brain does. Repetitive triggering of the stress response makes the amygdala more reactive to apparent threats, which stimulates the stress response, thereby further triggering the amygdala, on and on and on in a vicious cycle. The amygdala serves to help form “implicit memories,” traces of past experiences that lie beneath conscious recognition. As the amygdala becomes more sensitized, it increasingly tinges those implicit memoirs with heightened residues of fear, causing the brain to experience ongoing anxiety that no longer has anything to do with the circumstances at hand. At the same time, the hippocampus, which is critical for developing “explicit memories” —clear, conscious, records of what really happened—gets worn down by the body’s stress response. Cortisol and other glucocorticoids weaken synapses in the brain and inhibit formation of new ones. When the hippocampus is weakened, it’s much harder to produce new neurons and thus make new memories. As a result, the painful, fearful experiences the sensitized amygdala records get programmed into implicit memory, while the weakened hippocampus fails to record new explicit memories. When this happens, you wind up with no real memory of what set you off to begin with but with a very clear sense that something bad—something very bad—is happening. We have to transcend the body to change the body, overcome the ego to change the ego. We must become pure awareness and going beyond time, forget the known reality and go into the unknown and observe the infinite possibilities and tune into the possible realities, because if we think about them, in the quantum universe they already exist core, endurance, strength, neuroscience, the secrets for good longevity: heart health, brain health, muscle and joint health. Neuroscience and lagree method, besides fitness and wellness, neuro complex training. Happy to be part of this family and also to be its ambassador and researcher. also used by astronauts returning to earth.

Growth hormone’s impact on adipose tissue and aging

A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the healthspan and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormone.

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease.

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: •Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. •Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Prediabetes and mild hepatosteatosis are associated with blunted cortisol response to glucagon but not to growth hormone

BackgroundAlthough there is a close relationship between cortisol and growth hormone (GH) levels, glucose intolerance and hepatosteatosis, changes in GH and the hypothalamo-pituitary-adrenal (HPA) axis were not previously studied in prediabetes. The main purpose of the present study was to assess changes in GH and HPA axis and their relationship with hepatosteatosis in prediabetic patients. MethodsForty prediabetic patients, with body-mass index (BMI) 25–35kg/m2, and 23 healthy individuals, with normal glucose tolerance and similar age and BMI, were included. The 75g oral glucose tolerance test and glucagon stimulation test (GST) were used. ResultsNo significant differences were detected between prediabetic patients and healthy individuals in terms of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), IGF-1/IGFBP3 ratio or adrenocorticotropic hormone (ACTH). GH responses to GST did not differ between groups. On the other hand, peak cortisol and area under the curve (AUC) (cortisol) response on GST were significantly lower in prediabetic patients. Both peak GH and AUC (GH) response on GST correlated negatively with waist circumference and body weight. The degree of hepatosteatosis correlated negatively with peak cortisol, GH, AUC (cortisol) and AUC (GH) response on GST. ConclusionCortisol response to GST is decreased in prediabetic patients, with relatively well conserved GH response. This suggests altered HPA axis responsiveness in prediabetes, as is known in diabetes. Thus, HPA axis changes in patients with diabetes probably start before the development of diabetes as such.

Associations of GHR, IGF-1 and IGFBP-3 expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP) regulate growth and metabolic pathways. Using our Leipzig Adipose Tissue (AT) Childhood Cohort and Leipzig Atherobesity Childhood Cohort (n=306), we asked if serum levels of these factors are altered with overweight/obesity and if this is related to gene expression of these factors in AT cells and/or increased fat mass in childhood obesity. Furthermore, we hypothesized that gene expression of GHR, IGF-1 and IGFBP-3 in AT is associated with overweight/obesity and AT function in children. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio this obesity-related elevation was only detectable until early puberty. Circulating levels did not correlate with gene expression of these factors in AT cells, which was decreased with overweight/obesity. Independent from body mass index, gene expression of GHR, IGF-1 and IGFBP-3 in AT cells was related to parameters of AT dysfunction, such as adipocyte hypertrophy, and increased insulin levels. Serum GHBP was associated with the percentage of liver fat and transaminase levels. We conclude that the obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased subcutaneous AT mass and elevations in serum GHBP are more closely related to liver status in children. The diminished gene expression of these factors in AT cells with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

ODP299 Cabergoline Administration Markedly Improves Cognitive Impairment Associated with Macroprolactinoma

Abstract Introduction Prolactinomas classically present with galactorrhea, infertility, or hypogonadal symptoms. However cognitive impairment is rare presentation. We describe a man with a macroprolactinoma presenting with significant cognitive dysfunction which improved remarkably with cabergoline treatment. Case History A 21-year-old man with no significant past medical history presented to the hospital for evaluation of seizure-like activity. His father noted him limping earlier in the day and witnessed him fall and hit his head, while his brother reported involuntary convulsions and decreased awareness earlier that week. The patient himself had been complaining of blurry vision for 3 months for which he was prescribed glasses. Initial head CT demonstrated a 3.4×4.3×3.4cm cystic mass in the sella, 3.9×3.2×2.6 cm mass in the right basal ganglia and 2.7×2.3×3cm mass in the right temporal lobe. His prolactin was elevated at 16326 ng/mL. He was empirically started on dexamethasone due to concern for cerebral edema and was admitted. Surgery was recommended given the severity of his presentation, but the patient declined and he was discharged on cabergoline 1.5mg/week, dexamethasone taper, hydrocortisone 15mg/day, and levetiracetam 1000mg twice daily. On initial outpatient endocrinology evaluation 3 weeks later, he required the use of a wheel chair. Examination was notably for markedly flat affect, slurred speech, decreased attention span requiring frequent re-direction during the interview but he was otherwise oriented to person, time, and place. Neurological examination was noted for 4/5 muscle weakness throughout, facial asymmetry, decreased facial sensation, and an antalgic gait. He was recommended for expedited neurosurgical evaluation but he again declined. Laboratory drawn at this time showed a prolactin of 1946 ng/mL and total testosterone of 45 ng/dL, but he had normal thyroid and growth hormone axis (adrenal axis was not assessed as he was on dexamethasone taper). Carbergoline was titrated with further improvement in his prolactin levels. Four months after initial presentation, he reported enrolling in college with resolution of any cognitive and neurological deficits. Fourteen months after presentation, serum prolactin was 34 ng/mL on 4mg cabergoline per week and he is active in college and regularly plays basketball. Discussion Prolactinomas are incidentally detected or found as a result of workup for galactorrhea, infertility, or low libido. Typically, goals for treatment are to relieve compressive effects along the optic chiasm or to restore gonadal function. Acute cognitive decline should also be considered when there is a macroprolactinoma, and serial monitoring for improvement may be considered a clinical marker along with MRI imaging and prolactin levels. In this case, the patient had marked cognitive dysfunction on initial presentation but after 3 months of treatment had almost complete recovery as evidenced by his re-enrolling in college classes successfully. Presentation: No date and time listed

PMON49 Checkpoint Inhibitor Induced Hypophysitis with Growth Hormone Deficiency and Implications for the Treatment of ACTH Deficiency

Abstract Background/Purpose Hypophysitis is a known complication of immune checkpoint inhibitor (ICI) therapies used in the treatment of malignant cancers. In general, central adrenal insufficiency (AI) and hypothyroidism are the most recognized deficiencies following a diagnosis of ICI induced hypophysitis. As a result, other hypothalamic-pituitary axes (HPAs) are either incompletely evaluated or are disregarded from a therapeutic standpoint. Of particular importance is the growth hormone axis which is well established to affect tissue level metabolism of cortisol and cortisone through its effect on 11 beta hydroxysteroid dehydrogenase in target tissues. Our hypothesis is that growth hormone deficiency is also present in ICI induced hypophysitis. Methods We queried current and legacy electronic medical records of patients who received ICI for clinical notes mentioning adrenal insufficiency and concern for hypophysitis using the EMERSE tool. Patients with ICI exposure were included if they had 2 of the following 3 criteria; new onset central AI as defined by a low ACTH and cortisol, pituitary imaging suggestive of hypophysitis, or clinical presentation concerning hypophysitis. Patients were excludedfrom the analysis if there was a history of brain irradiation or in whom the diagnosis was not clear due to high dose steroid exposure prior to biochemical evaluation. Results Twenty-nine patients met inclusion criteria. Out of 29 patients, 16 underwent testing of the growth hormone axis with IGF-1 (11) and/or random growth hormone level (5). Seventeen patients (59%) had biochemical evidence of deficiency of 3 or more HPAs. Twenty-six patients (90%) had biochemical evidence of 2 or more PHAs. Two patients only underwent evaluation of 2 pituitary axes so it is unknown if they indeed suffered from panhypopituitarism. Most patients (28/29) were prescribed hydrocortisone for AI with an average dose of 20 mg per day. Conclusions Our findings are suggestive that growth hormone deficiency may be present in ICI induced hypophysitis. This finding holds implications for cortisol replacement therapy for coexisting AI. When one considers the average adrenal cortisol production is 5.7–7.4 mg/m2/day or 9.5–9.9 mg/day, 20 mg of daily cortisol replacementmay be too high in the face of concomitant growth hormone deficiency. Practice changes may include lower doses ofhydrocortisone replacement or adjustment to cortisone acetate which has been shown to have more favorable effectson tissue level metabolic effects. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP319 IGF-1 and BMI are Associated in Obese Patients with Acromegaly

Abstract Regulation of the growth hormone (GH) axis is complex and influenced by factors including age and nutritional status. Studies of individuals across the weight spectrum demonstrate an inverted U-shaped correlation between BMI and total IGF-1 levels; in both individuals with anorexia nervosa-range BMIs and those who are severely obese, total IGF-1 levels are low. Acromegaly is a disorder of the GH/IGF-1 axis characterized by IGF-1 excess secondary to autonomous GH secretion. The relationship between BMI and IGF-1 levels has not been well studied in acromegaly and whether the association between BMI and IGF-1 observed in non-acromegalic individuals is also present in acromegaly is not known. Patients who underwent endoscopic endonasal resection of pituitary adenomas at our institution between 1/2015-6/1/2021 were studied to investigate the association between BMI and preoperative IGF-1 in acromegaly. Ninety-nine patients were identified who either had evidence of preop biochemical hormone excess [elevated IGF-1 level and/or GH &amp;gt;1ng/ml following 75g oral glucose tolerance test] (n=40) or who had a clinically non-functioning, non-staining (NF) pituitary adenoma, or non-functioning GH-staining adenomas (n=59). We excluded anyone with a prior history of surgery/radiation, those on medical therapy (including somatostatin analogues, cabergoline), and those on oral contraceptives in the 3-months preceding surgery (n=8 in each group). Median age of acromegaly patients (n=32) was 39.5 years [29.3, 51.8], mean BMI was 30.2 +5.3 (SD) kg/m 2 (range: 20.9-40.4 kg/m 2) and 50% were female. Preoperative IGF-1 levels were measured using a clinically available assay. To control for differences in IGF-1 levels based on age/sex, we calculated % upper limit of normal (ULN) for IGF-1 based on age/sex determined normal ranges (mean %ULN IGF-1: 219.7+74.8%). In the acromegalic group, univariate analysis demonstrated a significant positive association between both BMI and IGF-1 (R=0.44, p=0. 01) as well as BMI and IGF-1%ULN (R=0.35, p=0. 047). In contrast, in the NF group (n=51 with 49% female and mean age: 56.4+16.7 years), there was no significant association between BMI (mean: 31.3+6.5 kg/m 2; range: 19.1-47 kg/m 2) and %ULN IGF-1 (median: 38.9% [26.8, 61.4]) (rho=0.15, p=0.30). However, in the subgroup of NF patients with severe obesity (BMI &amp;gt;35 kg/m 2; n=17), a significant inverse association between BMI and %ULN IGF-1 was observed (rho: -0.54; p=0. 03) . These data demonstrate that in contrast to the inverse relationship that is typically observed between total IGF-1 and BMI in obese individuals, which is preserved in a NF adenoma group, there is a significant positive association between %ULN IGF-1 and BMI in patients with acromegaly, including those with severe obesity. Further study is necessary to determine whether obese patients with acromegaly exhibit more severe symptoms related to their disease due to this positive association between BMI and IGF-1 or whether obesity is a secondary effect of their acromegaly. Presentation: No date and time listed

Predictive factors for recovery from adult growth hormone deficiency after transsphenoidal surgery for nonfunctioning pituitary adenoma.

Recovery from adult growth hormone deficiency (AGHD) after transsphenoidal surgery (TSS) has not been well discussed because of the lack of examinations including pituitary provocation tests (PPTs) before and after the procedure. This study aimed to evaluate the growth hormone (GH) axis function of patients with nonfunctioning pituitary adenoma (NFPA) via pre- and postoperative PPTs. Moreover, the predictive factors for recovery from AGHD after TSS were validated to facilitate surgery for AGHD in patients with NFPA. In total, 276 patients (median age 60.0 years) who underwent TSS for NFPA were included in this study. PPTs were performed before and 3 months after TSS. Then, the relationships between recovery from AGHD after TSS and clinical, surgical, and hormonal factors, including peak GH level based on PPTs, were evaluated statistically. In this study, 114 patients were diagnosed with preoperative AGHD. Approximately 25.4% recovered from AGHD after TSS. In contrast, among the 162 patients without preoperative AGHD, 13 (8.0%) had newly developed postoperative AGHD. The predictive factors for recovery from AGHD were younger age, female sex, initial TSS, and high peak GH level based on preoperative PPT. According to the receiver operating characteristic curve analysis, patients who were aged ≤ 62.2 years and had a peak GH level of ≥ 0.74 μg/L based on preoperative PPT were likely to recover from AGHD (sensitivity: 82.8%, specificity: 72.9%, and area under the curve: 0.8229). AGHD caused by NFPA can improve after initial TSS among young patients with certain peak GH levels assessed by preoperative PPT. Whether TSS for NFPA can promote recovery from AGHD is worth considering in some patients.

Crosstalk between Growth and Osmoregulation of GHRH-SST-GH-IGF Axis in Triploid Rainbow Trout (Oncorhynchus mykiss).

Smolting is an important development stage of salmonid, and an energy trade-off occurs between osmotic regulation and growth during smolting in rainbow trout (Oncorhynchus mykiss). Growth hormone releasing hormone, somatostatin, growth hormone and insulin-like growth factor (GHRH-SST-GH-IGF) axis exhibit pleiotropic effects in regulating growth and osmotic adaptation. Due to salmonid specific genome duplication, increased paralogs are identified in the ghrh-sst-gh-igf axis, however, their physiology in modulating osmoregulation has yet to be investigated. In this study, seven sst genes (sst1a, sst1b, sst2, sst3a, sst3b, sst5, sst6) were identified in trout. We further investigated the ghrh-sst-gh-igf axis of diploid and triploid trout in response to seawater challenge. Kidney sst (sst1b, sst2, sst5) and sstr (sstr1b1, sstr5a, sstr5b) expressions were changed (more than 2-fold increase (except for sstr5a with 1.99-fold increase) or less than 0.5-fold decrease) due to osmoregulation, suggesting a pleiotropic physiology of SSTs in modulating growth and smoltification. Triploid trout showed significantly down-regulated brain sstr1b1 and igfbp2a1 (p < 0.05), while diploid trout showed up-regulated brain igfbp1a1 (~2.61-fold, p = 0.057) and igfbp2a subtypes (~1.38-fold, p < 0.05), suggesting triploid trout exhibited a better acclimation to the seawater environment. The triploid trout showed up-regulated kidney igfbp5a subtypes (~6.62 and 7.25-fold, p = 0.099 and 0.078) and significantly down-regulated igfbp5b2 (~0.37-fold, p < 0.05), showing a conserved physiology of teleost IGFBP5a in regulating osmoregulation. The IGFBP6 subtypes are involved in energy and nutritional regulation. Distinctive igfbp6 subtypes patterns (p < 0.05) potentially indicated trout triggered energy redistribution in brain and kidney during osmoregulatory regulation. In conclusion, we showed that the GHRH-SST-GH-IGF axis exhibited pleiotropic effects in regulating growth and osmoregulatory regulation during trout smolting, which might provide new insights into seawater aquaculture of salmonid species.

Effects of zearalenone on ovarian development of prepubertal gilts through growth hormone axis.

This experiment aimed to establish the effects of zearalenone (ZEN) on ovarian development in prepubertal gilts through the growth hormone axis [growth hormone-releasing hormone (GHRH) / growth hormone (GH) / growth hormone receptor (GHR)]. In a 40-day experiment, 48 Landrace × Yorkshire crossbred prepubertal gilts were randomly allocated to four dietary treatments, including a basal diet supplemented with 0 (control), 400 (T1), 800 (T2), and 1,600 (T3) μg/kg ZEN. The ovary index of T2 (P = 0.058) and T3 (P = 0.065) increased compared to the control group. Besides, histopathological examination revealed that ZEN promoted the development of ovaries and follicles. The GHR content, relative expression levels of GHR, janus activated kinase 2 (JAK2) mRNA, and mean optical density of GHR in the ovaries of prepubertal gilts in the T2 experimental group increased significantly at P < 0.05 compared to the control group. The T3 group had significantly higher GHR content, relative JAK2 expression levels, and signal transducer and activator of transcriptions 3 (STAT3) mRNA. In conclusion, ZEN enhances the biological effect of GH, promotes the development of the ovary (follicle), and exerts reproductive toxicity by increasing the expression level of GHR, JAK2, and STAT3 mRNA ovary and immune intensity of GHR protein.

Brain, Lagree Method, Manual Therapy; Physical Exercise, Microformer, Massage in Psycho-Body, Emotional-Affective and Socio-Relational Recovery – Case Report for A Randomized Controlled Trial

Exercise as a moment of socializing, fun and well-being. Titanic Enterprise? Just want to do. For me, I have brought together the greatest, the best, my closest friends, for one great passion: movement, physical exercise, as a source of well-being, especially in this critical moment for those who have suffered damage even from the point of view economically. But the topic is another. I was in Sicily, a friend of mine is training with others but ... he has a herniated disc ... prevents him from moving ... yet, thanks also to the encouragement, the sociability, the fun of the group itself, he does not he feels pain and is able to perform all exercises perfectly. Hence the idea: can conviviality, sociality in the world of sport have and be a natural opioid? Can we modulate our perception of pain thanks to a “disembodied attitude and an inactive approach? We are embodied beings”, in which minds, bodies, environment and culture are connected to each other on different levels. “The answer is yes and the purpose of the post is to leave you breathless to admire the infinite beauty of my friends who train and have fun, live the sport , the Movement and long live true friendship. Obviously I emphasize my world, my fitness lagree method, Lagreefitness which also improves self-esteem, good mood through the generation of wellness molecules and hormones. Heart health, brain health, muscle and joint health. Neuroscience and lagree method; induction of the pituitary hypothalamic axis of growth hormone, its possible implications in longevity. The massage or touch is to give well-being through touch, body. A well-being not only physical, but also neural, social, rewriting neuronal circuits and improving synaptic plasticity. With this image I want to highlight the art of massage, manual techniques, rehabilitation and also movement and psychology. In a moment of uncertainty I want to give certainties; what we will return to instill well-being again. This is the topic of our research, indeed two. We scientifically demonstrate how both.

Efficacy of Growth Hormone in Chronic Kidney Disease

Children with chronic kidney disease (CKD) have difficulty achieving normal growth due to severe alterations in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis. Recombinant human growth hormone (rhGH) therapy (GH). It encourages long-term growth and allows children with CKD to reach normal height.It has been demonstrated to be both safe and effective. After a kidney transplant, growth retardation may remain. Multiple variables, such as steroid use, impaired renal function, and an aberrant GH axis, have contributed to this condition.

Synthetic growth hormone-releasing hormone agonist ameliorates the myocardial pathophysiology characteristic of heart failure with preserved ejection fraction.

To test the hypothesis that the activation of the growth hormone-releasing hormone (GHRH) receptor signalling pathway within the myocardium both prevents and reverses diastolic dysfunction and pathophysiologic features consistent with heart failure with preserved ejection fraction (HFpEF). Impaired myocardial relaxation, fibrosis, and ventricular stiffness, among other multi-organ morbidities, characterize the phenotype underlying the HFpEF syndrome. Despite the rapidly increasing prevalence of HFpEF, few effective therapies have emerged. Synthetic agonists of the GHRH receptors reduce myocardial fibrosis, cardiomyocyte hypertrophy, and improve performance in animal models of ischaemic cardiomyopathy, independently of the growth hormone axis. CD1 mice received 4- or 8-week continuous infusion of angiotensin-II (Ang-II) to generate a phenotype with several features consistent with HFpEF. Mice were administered either vehicle or a potent synthetic agonist of GHRH, MR-356 for 4-weeks beginning concurrently or 4-weeks following the initiation of Ang-II infusion. Ang-II-treated animals exhibited diastolic dysfunction, ventricular hypertrophy, interstitial fibrosis, and normal ejection fraction. Cardiomyocytes isolated from these animals exhibited incomplete relaxation, depressed contractile responses, altered myofibrillar protein phosphorylation, and disturbed calcium handling mechanisms (ex vivo). MR-356 both prevented and reversed the development of the pathological phenotype in vivo and ex vivo. Activation of the GHRH receptors increased cAMP and cGMP in cardiomyocytes isolated from control animals but only cAMP in cardiac fibroblasts, suggesting that GHRH-A exert differential effects on cardiomyocytes and fibroblasts. These findings indicate that the GHRH receptor signalling pathway(s) represents a new molecular target to counteract dysfunctional cardiomyocyte relaxation by targeting myofilament phosphorylation and fibrosis. Accordingly, activation of GHRH receptors with potent, synthetic GHRH agonists may provide a novel therapeutic approach to management of the myocardial alterations associated with the HFpEF syndrome.

Biomarkers of Environmental Enteric Dysfunction in Pregnancy and Adverse Birth Outcomes: An Observational Study Among Women Living With HIV in Tanzania

ObjectivesEnvironmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, may contribute to poor fetal growth in low-resource settings. Pregnant women living with HIV may be particularly susceptible to effects of EED, given their increased risk of infections and adverse birth outcomes. We sought to explore the associations of biomarkers of EED, inflammation and growth hormones with birth outcomes in pregnant women living with HIV in Dar es Salaam, Tanzania.MethodsWe performed a sub-study of 706 HIV-infected pregnant women participating in a randomized, double-blind, placebo-controlled trial assessing the effect of vitamin D3 supplementation. Maternal serum samples collected at 32 weeks gestation were analyzed for anti-flagellin and anti-LPS IgA and IgG via ELISA as well as using an 11-plex Micronutrient and EED Assessment Tool, which includes markers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14], systemic inflammation [C-reactive protein and α1-acid glycoprotein (AGP)], insulin-like growth factor 1 (IGF-1) and fibroblast growth factor 21 (FGF21). Biomarkers were categorized as quartiles. Associations with birth outcomes were assessed using linear regression analyses.ResultsPregnant women in the highest quartile of I-FABP had more than twice the risk of stillbirth compared to those in the lowest quartile (RR 2.43, 95% CI 0.98–6.03, ptrend = 0.02). Compared to women in the lowest quartile of AGP, those in the highest quartile gave birth to infants weighing 176g less (95% CI -280 to -71g, ptrend = 0.005). Maternal AGP was associated with increased risk of small-for-gestational age births; those in the highest quartile had a 70% greater risk compared to the lowest (RR 1.70, 95% CI 1.08–2.69, ptrend = 0.03). IGF1 was positively associated with birthweight and birthweight-for-age z-score; FGF21 was negatively associated with gestation duration and risk of preterm birth.ConclusionsMaternal biomarkers of EED, systemic inflammation, and the growth hormone axis were associated with birth outcomes. Further studies are needed to confirm these results and study the biologic mechanisms involved.Funding SourcesNational Institutes of Health (NICHD, NIDDK).

An appetite for growth: The role of the hypothalamic - pituitary - growth hormone axis in energy balance.

Links between the regulation of growth and energy balance are clear; to fuel growth, there must be consumption of energy. Therefore, it is perhaps intuitive that interactions between the hypothalamic – pituitary – growth hormone axis (growth axis) and pathways that drive metabolic processes exist. Overproduction of growth hormone has been associated with diabetes and metabolic disease for decades and the opposing effects of growth hormone and insulin have been studied since early experiments almost a century ago. The relationship between neuroendocrine axes can be complex and the growth axis is no exception, interacting with energy balance in several organ systems, both in the periphery and centrally in hypothalamic nuclei. Much is known about peripheral interactions between growth axis hormones and processes such as glucose homeostasis and adipogenesis. More is still being learned about the molecular actions of growth axis hormones in adipose and other metabolically active tissues, and recent findings are discussed in this perspective. However, less is known about interactions with central energy balance pathways in the hypothalamus. This perspective aims to summarise what is known about these interactions, taking lessons from human studies and animal genetic and seasonal models, and discusses what this may mean in an evolving landscape of personalised medicine.

Effects of the Isolated and Combined Ablation of Growth Hormone and IGF-1 Receptors in Somatostatin Neurons.

Hypophysiotropic somatostatin (SST) neurons in the periventricular hypothalamic area express growth hormone (GH) receptor (GHR) and are frequently considered as the key neuronal population that mediates the negative feedback loop controlling the hypothalamic-GH axis. Additionally, insulin-like growth factor-1 (IGF-1) may also act at the hypothalamic level to control pituitary GH secretion via long-loop negative feedback. However, to the best of our knowledge, no study so far has tested whether GHR or IGF-1 receptor (IGF1R) signaling specifically in SST neurons is required for the homeostatic control of GH secretion. Here we show that GHR ablation in SST neurons did not impact the negative feedback mechanisms that control pulsatile GH secretion or body growth in male and female mice. The sex difference in hepatic gene expression profile was only mildly affected by GHR ablation in SST neurons. Similarly, IGF1R ablation in SST neurons did not affect pulsatile GH secretion, body growth, or hepatic gene expression. In contrast, simultaneous ablation of both GHR and IGF1R in SST-expressing cells increased mean GH levels and pulse amplitude in male and female mice, and partially disrupted the sex differences in hepatic gene expression. Despite the increased GH secretion in double knockout mice, no alterations in body growth and serum or liver IGF-1 levels were observed. In summary, GHR and IGF1R signaling in SST neurons play a redundant role in the control of GH secretion. Furthermore, our results reveal the importance of GH/IGF-1 negative feedback mechanisms on SST neurons for the establishment of sex differences in hepatic gene expression profile.

A Comparison of the Blood Glucose, Growth Hormone, and Cortisol Responses to Two Doses of Insulin (0.15 U/kg vs. 0.10 U/kg) in the Insulin Tolerance Test: A Single-Centre Audit of 174 Cases.

Objective The insulin tolerance test (ITT) is the gold standard endocrine test used to assess the integrity of the growth hormone (GH) and cortisol axes. The ITT has potential risks, and severe hypoglycaemia may necessitate intravenous glucose rescue. There is no clear consensus as to the optimal insulin dose for the ITT. Therefore, we sought to compare the standard dose (0.15 U/kg) and a low-dose ITT (0.1 U/kg). Design Single-centre audit of ITT data (2012–2021). Patients and Measurements. Patients who underwent an ITT to assess possible GH deficiency/adrenal insufficiency were included. Glucose, GH, and cortisol were measured at baseline and 30, 45, 60, 90, and 120 minutes following I.V. insulin bolus (0.15 U/kg or 0.10 U/kg). Results Of the ITTs performed, only 3/177 (1.7%) did not achieve adequate hypoglycaemia (≤2.2 mmol/L) with a single insulin dose. In total, 174 patients (43.5 ± 12.1 yrs, mean ± standard deviation) were included for analysis (0.15 U/kg: n = 113, 0.10 U/kg: n = 61). All 174 subjects had adequate hypoglycaemia regardless of baseline fasting blood glucose level or insulin dose. Neither nadir glucose nor glucose delta (i.e., baseline minus nadir) differed between insulin doses. Trends in both cortisol and GH responses over time were similar between groups, and a greater proportion of patients receiving the standard dose had an adequate cortisol response (77/106 (72.6%) vs. 32/60 (53.3%), p=0.01). The rates of glucose rescue did not differ in a subset of 79 patients, with on-demand glucose rescue in 4/35 (11%) for the standard dose and 2/44 (5%) for the low dose (p=0.25). Conclusions Our results suggest that the low-dose ITT produces comparable glucose, cortisol, and GH responses to the higher dose. Given the risks associated with hypoglycaemia, the low dose appears to be preferable to the standard dose ITT in most circumstances.

Investigation of pituitary functions after acute coronavirus disease 2019.

Although coronavirus disease 2019 (COVID-19) mainly involves the lungs, it also affects many systems. The hypothalamic/pituitary axis is vulnerable to hypoxia, hypercoagulation, endothelial dysfunction and autoimmune changes induced by COVID-19 infection. Given that there is no extensive investigation on this issue, we investigated the pituitary functions three to seven months after acute COVID-19 infection. Forty-three patients after diagnosis of COVID-19 infection and 11 healthy volunteers were included in the study. In addition to the basal pituitary hormone levels, growth hormone (GH) and hypothalamo-pituitary adrenal (HPA) axes were evaluated by glucagon stimulation test (GST) and low-dose adrenocorticotropic hormone (ACTH) stimulation test, respectively. The peak cortisol responses to low-dose ACTH test were insufficient in seven (16.2%) patients. Twenty (46.5%) and four (9.3%) patients had inadequate GH and cortisol responses to GST, respectively. Serum insulin-like growth factor-1 (IGF-1) values were also lower than age and sex-matched references in four (9.3%) patients. The peak GH responses to GST were lower in the patient group when compared to the control group. Other abnormalities were mild thyroid-stimulating hormone elevation in four (9.3%) patients, mild prolactin elevation in two (4.6%) patients and central hypogonadism in four (9.3%) patients. Mean total testosterone values were lower in male patients when compared to male controls; however, the difference was not significant. These findings suggest that COVID-19 infection may affect pituitary functions, particularly the HPA and GH axes. These insufficiencies should be kept in mind in post-COVID follow-up. Long-term data are needed to determine whether these deficiencies are permanent or not.

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family.

Background: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease that is caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). Functional analysis of the mutated receptor is necessary to verify the impact of the mutation on receptor function and suggest some possible therapeutic strategies for specific functional defects.Methods: Family history and clinical information were collected. Whole-exome sequencing and sanger sequencing were performed to determine the potential genetic cause of diabetes insipidus. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. Bioinformatic analysis was performed to predict the function of the identified variation. Moreover, wild-type and mutated AVPR2 vectors were constructed and transfection to HEK-293T cells. Immunofluorescence experiments were performed to investigate the expression and localization of the mutated protein and cAMP parameter assays were used to measure its activity in response to AVP.Results: The heights of the adult members affected with polyuria and polydipsia were normal, but all affected children had growth retardation. Next-generation sequencing identified a novel mutation in AVPR2 gene (c.530T > A) in this family. Bioinformatic analysis indicated that the mutation in AVPR2 changed the hydropathic characteristic of the protein and was probably deleterious. Although immunofluorescence showed that the mutated AVPR2 was normally expressed in the cell surface, the intracellular cAMP concentration stimulated by AVP was significantly lower in cells transfected with mutated AVPR2 than cells transfected with wild-type AVPR2. Based on the ACMG criteria, the novel c.530T > A variant of the AVPR2 gene was likely pathogenic and the affected family members were diagnosed as CNDI. After the confirmation of the diagnosis, the proband was treated with compound amiloride hydrochloride and rhGH, the symptoms of polyuria, polydipsia and growth retardation were all improved.Conclusion: These findings suggested that the novel mutation in AVPR2 (c.530T > A) was a true disease-causing variant with mild effects, which could be classified as a type III mutant receptor. Moreover, investigations of the function of growth hormone axis could be important for the pediatric CNDI patients with extreme short stature, and rhGH treatment might improve the final adult heights in these patients.